Phosphoric, phosphonic, phosphinic, thionophosphoric, -phosphonic,-phosphinic acid esters



United States Patent 13 Claims. cl. 260-949) This application is acontinuation-in-part of application Ser. No. 331,121 filed Dec. 17,1963, now abandoned, in the names of the instant inventors.

The present invention relates to and has as its objects new and usefulpesticidally, especially insecticidally active phosphorus containingcompounds.

More specifically this invention has as its objects phosphoric,phosphonic, phosphinic, thionophosphoric, -phosphonic, -phosphinic acidesters of the general formula nix SR Q P-O- as well as a process for theproduction of those compounds. In the above formula, R represents astraightchain or branched optionally substituted alkyl or an optionallysubstituted cycloalkyl or aryl radical, whilst R and R" denoteoptionally substituted alkyl, alkenyl, cycloalkyl, aralkyl, or arylradicals, which may be linked directly to the phosphorus atom or viaoxygen, sulphur, or nitrogen. R and R" may in addition representoptionally N-substitutcd amino groups, X denotes an oxygen or sulphuratom and the index n has a value of zero, 1, or 2.

The symbol R preferably represents a methyl, methoxycarbonylmethyl,ethyl, hydroxyethyl, propyl, isopropyl, n-butyl, cyclohexyl, isooctyl,or n-dodecyl group, and also a phenyl, chlorophenyl, methylphenyl,methoxyphenyl, or nitrophenyl radical, whilst R and R preferably denotemethyl, ethyl, chloromethyl, isopropyl, isobutyl, iso octyl,methoxyphenyl, ethylthiophenyl, benzyl, phenyl, chlorophenyl, andmethoxyphenyl radicals, and also methoxy, ethoxy, isopropoxy,chloroethoxy, methylmercapto, ethylmercapto, isopropylmercapto,chloroethylmercapto radicals as Well as monoor di-methyl-(-ethyl-,-cyclohexyl)-amino groups.

It has been found that compounds of the above stated structure areobtained smoothly and in good yields when (thiono-)-phosphoric-(phosphonic, phosphiuic) acid ester monohalides of thegeneral formula are reacted with mono-alkyl-, -cycloalkylor-aryl-mercapto-(-sulphoxido-, -sulphono-)-mono-nitrophenols of theformula "Ice In the last-mentioned formulae, the symbols R, R, R", X andn have the above stated significance, whereas Hal denotes a halogenatom.

The following phenols may be mentioned as examples of those suitable forthe reaction according to the invention:

3-methylmercapto-4-, 3-ethylmercapto-4-, S-isopropylmercapto-2-, 5butylmercapto-2-, 5-isooctylmercapto-2-, 3-dodecylmercapto-4-,3-phenylmercapto-4-, 3-methoxypheuylmercapto-4-,5-chlorophenylmercapto-2-, 3-p-tolylmercapto-4-, and5-nitrophenylmercapto-Z-nitrophenol, as well as 3-methylsulphoxyl-4- and3-ethylsulphonyl-4-nitrophenol.

The process according to the invention is preferably carried out in thepresence of inert organic solvents, among these, optionally chlorinatedaliphatic or aromatic hydrocarbons, alcohols, as well as low boilingaliphatic ketones, such as acetone, methyl ethyl ketone, methylisopropyl ketone, or methyl isobutyl ketone and nitriles, such asacetonitrile and propio-nitrile, as well as dimethylformamide have,inter alia, proved suitable.

In addition, the preparation of the (thiono-) phosphoric (-phosphonic,-phosphinic) acid esters according to the invention is preferablycarried out in the presence of acid binding agents, among which alkalimetal alkoxides and carbonates as well as tertiary amines areparticularly suitable. However, it is just as possible to prepare thesalts, preferably the alkali metal salts, of the above mentioned phenolsand subsequently to react these with the above mentioned(thiono-)-phosphoric (-phosphonic, -phosphinic) acid ester halides inaccordance with the process of the invention.

The reaction according to the process already takes place at roomtemperature, but it has proved convenient to carry out the reaction atslightly to moderately elevated temperatures and also to continueheating the reaction mixture for some time, with stirring, after thestarting components have been combined. In that case, the products ofthe process are obtained in particularly good yields and also withexcellent purity.

The monoalkyl-, -cycloalkylor -aryl-mercapto-mononitro-phenols requiredas starting materials for the reaction according to the invention andnot hitherto known from the literature can be prepared by reacting thecorresponding rnonochloro-mono-nitro-phenols with a mercapto compound ofthe general formula RSH, wherein R has the same significance as givenabove, said reacting being effected in a liquid medium in the presenceof an inorganic base in the reaction mixture at a temperature of 0 to C.and isolating the monomercapto-mononitrophenols from the liquid medium.

Some of the (thiono-)phosphoric (-phosphonic, phosphinic) acid estersaccording to the invention constitute well crystallised substances witha sharp melting point, which can readily be further purified byrecrystallisation from the usual solvents; however, some of the productsare also obtained in the form of viscous oils which can not be distilledwithout decomposition even at strongly reduced pressures.

The products are characterised by a very good pesticidal activity,particularly by an excellent insecticidal action, and are thereforeemployed as pest control agents, especially in plant protection.

The new compounds of the present invention very effectively kill insectslike aphids, spider mites, caterpillars, fiies, ticks, etc. Theydistinguish themselves especially by a good contact-insecticidalactivity and mostly also by a systemic action. At the same time theyhave an activity on eating insects such as caterpillars. Mostsurprisingly they are of remarkably low toxicity against warmblooded-animals.

The application of the compounds according to the invention for theabove stated purpose is carried out by the method usual for insecticidesbased on phosphoric acid esters, i.e., in a concentration from about0.00001% to about 1%, diluted or extended with suitable solid or liquidcarriers or diluents. Examples of such solid carriers are talc, chalk,bentonite, clay and the like, as liquid carriers there may be mentionedwater (if necessary with commercial emulsifiers), alcohols, especiallylower alcohols such as methanol or ethanol, ketones, especially lowerketones such as acetone or methyl ethyl ketone, liquid hydrocarbons andthe like. The new compounds may furthermore be used in combination witheach other or with known insecticides, fertilizers, etc.

As examples for the special utility the inventive compounds of thefollowing formulae S H murmur-o-Qscrn have been tested against aphids(compounds II and III), spider mites (compound III), caterpillars(compounds II and III) and mosquito larvae (compounds I and II). Aqueousdilutions of these compounds have been prepared by mixing the activeingredients with the same amounts of dimethyl formamide as an auxiliarysolvent adding thereto 20% by weight referred to active ingredient of acommercial emulsifier consisting of a benzyl hydroxy polyglycol ethercontaining about to glycol ethers, and diluting this premixture at lastwith water to the desired concentration indicated in the followingparagraphs. The tests have been carried out as follows:

(a) Against aphids (species Doralis fabae): heavily infested bean plants(Vicia faba) have been sprayed drip wet with solutions as preparedabove. The eifect has been determined after 24 hours by counting thedead pests either on the surface of the soil or still remaining on theplants. The following results have been obtained:

Aqueous concentration Killing rate Compound (in percent active (inpercent) ingredient/water) II 0. 01 90 III 0. 001 98 Compound IIIAqueous concentration (in percent active ingredient/Water) 0.00 1

Killing rate (in percent) 98 (0) Against caterpillars of the typediamond black moth (Plutclla maculiperznis): white cabbage has beensprayed drip wet with aqueous emulsions as prepared above in aconcentration as shown below. Caterpillars (10 each) have been placed onthe sprayed leaves of the white cabbage. The living status has beendetermined after 24 and 48 hours. The following results have beenobtained:

Killing rate Aqueous concentration (1n percent) Compound (in percentactive ingredient/water) II 0. 01 100 III 0. 001 100 Aqueousconcentration Killing rate Compound (in percent active (in percent)ingredient/water) I 0. 000001 100 II 0.0000001 60 The following examplesillustrate the invention:

Example 1 SCH 18.5 g. (0.1 mole) of 3-methylmercapto-4-nitrophen0l (M.P.!175 to 176 C.) are stirred together with 15.2 g. of anhydrous potassiumcarbonate at 60 C. for one hour in 100 ml. of dry methyl ethyl ketone.18.8 g. of 0,0-diethylthionophosphoric acid ester chloride aresubsequently added dropwise to the reaction mixture and the latter isheated at 60 to 70 C. for another hour. After the mixture has beencooled to room temperature, the separated salts are filtered oif withsuction and washed with methyl ethyl ketone. The filtrate is combinedwith the wash liquor and poured into 1 litre of ice-water, whereupon theseparated oil solidifies in the form of crystals within a short time.The crystals are filtered off with suction, washed with water, anddried. The 0,0-diethylthionophosphoric acid-O-(3-methyl-mercapto 4nitrophenyl-) ester (30 g., corresponding to 91% of the theoreticalyield) obtained by this method is recrystallised from methyl-cyclohexaneand then has a melting point of 61 to 62 C. The yield of pure productamounts to 28.6 g., corresponding to of the theoretical.

Analysis.Calcd.: P, 9.2%; S, 19.0%; N, 4.15%. Found: P, 9.2%; S, 18.9%;N, 4.45%.

destruction of aphids and destruction of leaf beetles is caused by0.001% solution of the compound. Moreover, 0.1% solution of the producthave a 100% systemic activity towards aphids.

\ SCH:

18.5 g. (0.1 mole) of 3-methylmercapto-4-nitrophenol, 15.2 g. ofpotassium carbonate, and 17.6 g. (0111 mole) of0,0-dimethyl-thionophosphoric acid ester chloride are reacted in methylethyl ketone in the same manner as described in Example 1. The oil whichseparates when the reaction mixture is poured into water is taken up inben zene, the benzene solution is Washed with water until its reactionis neutral, and it is dried over sodium sulphate. When the solvent hasbeen evaporated off in vacuo, 28.3 g. (91.5% of the theoretical yield)of 0,0-dimethyl-thionophosphoricacid-O-(3-methylmercapto-4-nitr0phenyl-) ester remain in the form of abrown oil.

Analysis.Calcd.: P, 10.1%; S, 20.7%; N, 4.53%. Found: P, 10.4%; S,20.85%; N, 4.73%.

The mean toxicity of the compound on rats per os amounts to 250 mg. perkg. of animal. Mosquito larvae are killed 100% by 0.000001% solution ofthe ester.

CIIsO The 3 methylmercapto 4 nitrophenol to be used as starting materialis prepared in accordance with the general statements given above in thefollowing way:

173.6 g. (1 mole) of 3-chloro 4 nitrophenol are dissolved in 300 m1. ofethanol, and a solution of 80 g.

6 acetate/benzene mixture (1:2) in orange needles of M.P. 175 to 176 C.

Analysis.C- H NO S (molecular weight 185.2). Calculated: C, 45.41%; H,3.81%; N, 7.57%; O, 25.92%; S, 17.28%. Found: C, 45.41%; H, 3.76%; N,7.73%; 0,

of sodium hydroxide in 550 m1. of water is added to the 5 25.54%; S,17.4%, molecular weight 190. mixture with cooling and stirring. 24.6litres (1.1 mole) The following compounds can be obtained under the ofgaseous methyl-mercaptan is then introduced into the same reactionconditions: reaction mixture at 5 to C., with cooling, and the Yieldreaction mixture is boiled under reflux for 3% hours at Constitution(percent Physical an internal temperature of C., a dark red solution be-10 gg g Pmpmies ing formed. The solution is cooled to 60 C. andacidified to pH 2 to 3 by adding about 210 ml. of 20% hydrochloric SC Hacid dropwise. This precipitates 3 methyl mercapto-4- c o p 2 5 Brownnitro-phenol in the form of orange crystals. Precipitation 15 iscompleted by slowly cooling the mixture to +10 C. 3 methyl-mercapto 4nitrophenol is filtered off by I suction, washed With water and dried invacuo. Yield: The mean toxlclty the compound amounts to about 170 g. of3 methylmercapto 4 nitrophenol M.P. 300 a p of ammal, p Orally on the m100% 174.5 to 175.5 C. (this corresponds to 92% of the destruction ofmosquito larvae is caused by 0.000001% theoretical yield). The compoundcrystallises from an ethyl solutions of the product. s

Constitution Yield (percent 01 Physical properties the-theoreticall- /0SC H I (GIH6O)IP 2 5 80.5 Brown 011.

O -NO:

SCH: (l-C 3H7O)EP 87. 7 Light brown 011.

S 0 2 5 11/ SCH: CH -P\ l 86 Brown oil.

I fi/ so H oH=P 2 5 85.5 Brown oil.

S S04E11 (0 11 0) P\ 83. 2 Yellow-brown 011.

s SC4HB (CH3O)2P 77. 5 Yellow-brown oil.

S u 2s zHa h 80 Light brown 011.

S S n u (CH O)P 4 63 Light brown 011.

' SCH: (C.1.C.HET.CHZO)1;E\ Bmwn o No,

S COzH C H 5 Light brown 011. v \O l IO2 CHaO /O SCH \P/ l a 18 02.10.:P, 9.3%; N, 8.4%. Found; P, 9.6%; N, 8.0%. (CgHQzN O- NO9 ConstitutionYield (percent of Physical properties the theoretical) 011 mm l 67.30316.; P, 3.3%; N, 3.3%.

\ Found: P, 3.0%; N, 4.0%.

(C7H5O)2P 90.3 0810.: P, 7.3%; s, 16.0%.

\ Found: P, 3.2%; s, 15.9%.

O -NO:

0 S (C,H 0)1P 91. 5 M.P.; 56 to 53 0.

\ Cale; P, 3.1%; N, 3.7%.

O NO: Found: P, 8 3 3.6%.

s p S CH3 (C HEOMP 69. 4 M.P.: 69 to 71 c.

\ Ca1c.; P, 7.5%; N, 3.4%.

0- -NO: Found: P,74 ,3.5%.

(IJHr S S (CgHgOhP 92 M.P.; 65 to 66 0.

O-- NO: Found: P, 7.65%; N, 3 6% (C2H O)1P 81 03.10.: P, 7.5%; N, 3.4%.

\ Found: P, 7.7%; N, 3.5%.

O N(): CH3

S 3 -01 (CgH5O)gP 95 M.P. 63 to 65 0.

0 NO2 Found; ,7.4%;c1,s.3%.

( 2H5 )zP 92. 5 0310.: P, 7.2%; S, 14.9%.

\ Found; P, 7.3%; s, 15.0%.

O NO: 1

l S a 4 (c H ohP 96 Ca1c.: P, 7.6%; s, 15.3%; C,

O NO:

Foundz'P, 7.55%; S, 15.9%;

SCHrCOOCH; (CZHQOMP l 82 Cale P, 7.85%, N, 3.55%.

\ Found; P, 8.15 3.7%.

Example 3 The following compound is obtained by the same 0 method:

SCI-Ia I Yield (per- Physical O NO Constitutwn cent of the properties 2theoretical) 18.5 g. (0.1 mole) of 3-methylmercapto 4 nitro- 50,115phenol, 15.2 g. of potassium carbonate, and 18.6 g. of z a )z l 77 M.P.:42-44". 0,0-diethylphosphoric acid ester chloride are reacted in 0methyl ethyl ketone inathe same way as described in Example 1. The oilobtained when the mixture is worked 7 The means toxicity of the compoundon rats per os amounts to 50 mg. per kg. of animal. Caterpillars are100% destroyed and aphids are destroyed by 0.01% solution, and mosquitolarvae are still 60% killed by 0.0000001% solution of the ester.

'9 x Example 4 SCHa 14 g. of dimethyl-thionophosphinic acid esterchloride are added dropwise at 40 to 50 C. to a mixture of 18.5 g. (0.1mole) of 3 methylmercapto 4 nitrophenol, 15.2 g. of potassium carbonate,and 100 ml. of acetonitrile. The mixture is subsequently stirred at 50to 60 C. for another 2 hours. After it has been cooled to roomtemperature, the mixture is poured into 1 litre of icewater, theseparated crystalline product is filtered oil with suction, washed Withwater, dried, and recrystallised from n-propanol. Thedimethyl-thionophosphinic acid O (3- methylmercapto 4 nitrophenyl-)esternow melts at 78 C. The yield amounts to 67.5% of the theoretical.

Example 5 yl-thionophosphoric acid O (3-n-propylmercapto-4-nitrophenyl-)ester, corresponding to 84.5% of the theoretical yield, areobtained in the form of a brown oil.

The following compounds can be prepared by the same method.

9.2 g. (0.05 mole) of 2-nitro-5-methylmercaptophenol (M.P. 179 to 180C.) are reacted in the presence of potassium carbonate with 11.5 g.(0.055 mole) of 0,0- dimethyl-thionophosphoric acid ester chloride in 50ml.

of anhydrous acetone in the sameway as described in Example 1. Thereaction product which is obtained in the form of crystals is filteredoff with suction, washed 10 with water, and dried over sodium sulphate.The yield of 0,0 dimethyl thionophosphoric acid-O (2-nitro-5-methylmercapto-phenyl-)ester amounts to 92% of the theoretical. Whenrecrystallised from methylcyclohexane, the compound melts at 62 C.

The 2-nitro-5-methylmercaptophenol necessary as starting material isproduced by the following method:

173.6 g. .(1 mole) of 2-nitro-5-chlorophenol are suspended in 500 ml. ofwater and a solution of g. (2 mole) of sodium hydroxide in 600 ml. wateris added with stirring. 24.6 litres (1.1 mole) of gaseous methylmercaptan are introduced into this mixture and the latter is then heatedfor 4 hours under mild reflux. After acidifying the reaction mixturewith 20% hydrochloric acid to pH 2 to 3, the mixture is cooled to 10 C.and 2-nitro-5- methylmercaptophenol which has precipitated in the formof dark crystals is removed by suction filtration. A small quantity ofproduct may still be removed in the form of oil from the filtrate andcrystallised from benzene/ ligroin. The yield amounts to 146 g.Z-nitro-S-methylmercapto-phenol (79% of the theoretical).

The compound crystallises from benzene/ligroin-mixture in the form ofyellow brown needles of M.P. 75 C. to 76 C.

Analysis.C H7NO S (molecular weight 185.2). Calculated: C, 45.41%; H, 3.81%; N, 7.57%; 0, 25.92%; S, 17.28%; molecular weight 185.2. Found: C,45.46%; H, 3.94%; N, 7.71%; O, 25.99%; S, 17.29%; molecular weight 188.

Example 7 18.5 g. of 3-methylmercapto-4-nitrophenol and 15.2 g. ofpowdered potassium carbonate in ml. of methyl ethyl ketone are reactedwith 17.9 g. of bis-(N,N-dimethylarnido)-phosphoric acid chloride asdescribed in Exam- 66% of the theoretical yield, are obtained intheformof a brown oil.

Example 8 S (CzHnOhP l 18.5 g. (0.1 mole) of3-nitro-4-methylmercaptophenol (M.P. to 116 C.) and 21.1 g. (0.105 mole)of 0,0-

diethyl-thionophosphoric acid ester chloride are reacted in the presenceof 15.2 g. (0.11 mole) of anhydrous potassium carbonate in the samemanner as described in Example 1. After Working up the reaction mixturethere are .obtained 31 g. corresponding to 92% of the theoretical yieldof 0,0-diethylthionophosphoric acid-O-(3-nitro-4-.

methylmercapto-phenyl-)ester in the form of a light brown oil. 7

Analysis-Cale: P, 9.2%; S, 19.0%; N, 4.15%; Found: P, 9.1%; S, 19.1%; N,3.9%.

Caterpillars are completely destroyed by 0.001% solutions of thecompound, aphids and spider mites are still killed 98%. Uponadministration against spider mites the product is also ovicidallyactive.

In an analogous manner there can be prepared the following compounds:

Yield (percent Constitution of th s1 )theoreti- Physical properties s N2 '(C2H'5O)2P\ 72. 2 1049 s,

I1 O SCH2CH;OH Ou Example9 wherein R and R stand for lower alkyl havingup to 4 S 10 carbon atoms and R stands for alkyl having up to 12 car- Nbon atoms. (CZHEO) I 5. A compound of the formula Q R, 1=o s R 9.25 g.(0.05 mole) of Z-methylmercapto-S-mtrophenol (MIP- 146 to 147 C.) and 11g. of 0,0-diethyl-thiono phosphoric acid ester chloride are reacted inthe presence h i R d R t d f lower alkyl having up to 4 0f of Potassiumcarbonatfi described 111 l 20 carbon atoms and R stands for alkyl havingup to 12 car- 1 and there are obtained after working up the reaction hatoms, mixture 16 g. Of 0,0-diethyl-thionophosphoric acid-O (2- 6 Thecompound of the formula methylmercapto-S-nitrophenyl-)ester of meltingpoint 60 to 62 C. on o s scam-i Example 10 3 Q CHaOPO N02 t s-CH (mmOhPia 7. The compound of the formula l O N O 20.1 g. (0.1 mole) of3-methylsulphoxido-4-nitrophenol 2 (prepared in usual manner byoxydation of B-methylmer- 021150 capto-4-nitrophenol with hydrogenperoxide) are reacted I with 21.1 g. 0.105 mole) of0,0-diethyl-thionophos- The the formula phoric acid ester chloride inthe presence of 15.2 g. (0.11 S0113 mole) of potassium carbonate in thesame manner as deaO s I scribed in Example 1. There are obtained 30 g.,corre- {L sponding to 87.5 g. of the theoretical yield, of 0,0-diethyl-40 OH thionophospho-ric acid-O-(3-methyl-sulphoxido-4-nitro- 3phenyl-)ester in a crystalline form. M.P. 49 to 51 C. 9 The compound fthe f l Analysis.Calc.: P, 8.8%; S, 18.2%; N, 4.0%. Found: P, 9.0%;S,18.3%;N, 4.15%. 0 80213 What we claim is: CH3 fi 1. A compound of theformula 0 N0:

R1 X SR OHaO 10. The compound of the formula R: N 02 S OH 0211 0 0wherem R and R stand independently for members se- \II 0 lected from thegroup consisting of alkyl having up to 8 carbon atoms, phenyl, loweralkoxy having up to 4 car- CZHSO bon atoms and monochloro lower alkoxyhaving up to 4 55 carbon atoms, R stands for a member selected from theThe compound of the formula group consisting of alkyl having up to 12carbon atoms, SCaH n lower alkoxy-carbonyl substituted lower alkyl, saidlower 01130 3 alkoxy and lower alkyl having up to 4 carbon atoms and NOhydroxy substituted lower alkyl having up to 4 carbon atoms, and Xstands for oxygen or sulfur. CHaO 2. The compound according to claim 1wherein R Th and R stand for lower alkoxy having up to 4 carbonecompound of the formula atoms and R stands for alkyl having up to 12carbon atoms. CH3O\IS I 3. The compound according to claim 1 wherein RIO-SCaH1-iso stands for alkyl having up to 8 carbon atoms, R stands01130/ for lower alkoxy having up to 4 carbon atoms and R stands foralkyl having up to 12 carbon atoms. 13, Th compound f h f l 4. Acompound of the formula NO SR CzHsO S 2 0 s i \H R /PO SCH3 /P O NO2C2H5O R20 (References on following page) References Cited UNITED STATESPATENTS Kosolapoff 167-30 Mattson 167-30 Thompson 260-461 Farrar 260-461Schegk et a1 260-949 Sirrenberg et a1. 260-949 X 16 FOREIGN PATENTS216,205 9/195 6 Australia, 560,179 9/1957 Belgium. 903,429 8/ 1962 GreatBritain.

CHARLES B. PARKER, Primary Examiner.

R. L. RAYMOND, Assistant Examiner.

1. A COMPOUND OF THE FORMULA